Fas is a death receptor belonging to the TNFR superfamily and induces
cell apoptosis by both activating a caspase cascade and altering mitochondria.

In the immune system, Fas is involved in the switching-off of the immune
responses and cell mediated cytotoxicity.

In humans, genetic defects decreasing
Fas function cause the Autoimmune Lymphoproliferative Syndrome (ALPS) where
autoimmunities are associated with accumulation of polyclonal lymphocytes
in the secondary lymphoid tissues and expansion of T cells lacking both
CD4 and CD8 (DN cells).

Expansion of DN cells is absent in an ALPS variant,
named Dianzani's Autoimmune Lymphoproliferative Disease (DALD).

The observation
that DALD patients' families display increased frequency of autoimmune
diseases different from ALPS suggests that defects of Fas function may
also play a role in development of "common" autoimmune diseases.

This possibility
is supported by detection of defective Fas function in substantial proportions
of patients with the multiple autoimmune syndrome or aggressive forms of
type 1 diabetes or multiple sclerosis.

This article reviews data suggesting
that development of autoimmune/lymphoproliferative patterns may involve
several alterations hitting the Fas system, but might also involve alterations
in other systems contributing to the switching-off or proliferation of
lymphocytes.